Health TrialsbyHealthPanel

BGB-58067 in Newly Diagnosed Glioblastoma Patients With MTAP-Deleted Tumors

ConditionGlioblastoma (GBM)
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNader Sanai

About this trial

This is an open-label, multi-center, Phase 0/2 trial designed to enroll up to 78 total participants with suspected newly diagnosed glioblastoma (nGBM) who are scheduled for surgical resection to accrue at least 14 participants in Arm A and 10 participants in Arm B. The trial will evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of BGB-58067.

The study is composed of a Phase 0 and expansion Phase 2 component. The Phase 0 primary endpoint will be suppression of symmetric dimethylarginine (SDMA) in tumor tissue measured by immunohistochemistry (IHC). The Phase 2 primary endpoint will be 12-month overall survival rate (OS12).

The Phase 0 secondary endpoint will be to characterize the PK of BGB-58067 in tumor tissue, plasma, and cerebrospinal fluid (CSF). The Phase 2 secondary endpoints will include assessing the safety profile of BGB-58067 and evaluating clinical efficacy of BGB 58067 using overall survival (OS) and the 6-month progression-free survival rate (PFS6) estimated by Kaplan-Meier (K-M) methods.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

1. Suspected newly diagnosed glioblastoma according to 2021 WHO criteria who have not received any tumor directed intervention other than biopsy.

2. Has measurable disease (preoperatively), defined as at least one contrast-enhancing lesion with two perpendicular measurements of at least 1 cm.

3. Age ≥ 18 at time of consent.

4. Has a performance status of ≤ 2 on the ECOG scale.

Disqualifiers

1. Unable to undergo MRI of the brain with intravenous (IV) contrast.

2. Has a known active systemic bacterial infection (on IV antibiotics or has fever > 38.5°C at time of initiating study treatment) or fungal infection, or has a detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [e.g., hepatitis B surface antigen positive]). NOTE: Screening of viral infection is not required for enrollment.

LVEF < 50%

History of prolonged QTc, or QT interval corrected for heart rate using Fridericia's formula (QTcF) prolongation > 480 msec, except for right bundle branch block.

Trial design

Design model

Parallel

Treatments tested in this trial

  • BGB-58067

    Drug

    During Phase 0, a high dose of BGB-58067 will be administered over several days prior to surgery to determine PK and PD effect in resected tumor tissue. During Phase 2, BGB-58067 dosing will continue with standard radiation therapy (RT) followed with adjuvant therapy. Participants will receive monotherapy or concurrent therapy with temozolomide (TMZ) based on MGMT methylation status.

Treatment groups

78 Participants
are divided into 2 treatment groups
Group A: Arm A: Unmethylated-MGMT GBM-BGB-58067 MonotherapyExperimental treatment 1 intervention
Group B: Arm B: Methylated-MGMT GBM-BGB-58067 + TMZ Concurrent TherapyExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Phase 0: Proportion of Participants with ≥ 50% Decrease from Baseline in SDMA Expression, or with SDMA H-Score ≤ 70, in Phase 0 Tumor Tissue Collected Intraoperatively

Decrease in SDMA expression in tumor tissue collected during Phase 0 surgery relative to baseline will be used if pre-treatment biopsy tissue is available. Otherwise, H-score ≤ 70 in tumor tissue collected during Phase 0 surgery will be used.

Time frame
Intraoperatively
2

Phase 2: Proportion of Participants Alive at 12 Months

Overall survival at 12 months (OS12)

Time frame
Date of Phase 0 surgery to date of death due to any cause, assessed up to 12 months

Secondary outcomes

1

Phase 0: Mean Total Concentration of BGB-58067 in Gadolinium Enhancing and Non-Enhancing Tumor Tissue

Tumor tissue collected during Phase 0 surgery

Time frame
Intraoperatively
2

Phase 0: Mean Unbound Concentration of BGB-58067 in Gadolinium Enhancing and Non-Enhancing Tumor Tissue

Tumor tissue collected during Phase 0 surgery

Time frame
Intraoperatively
3

Phase 0: Median Total Concentration of BGB-58067 in Gadolinium Enhancing and Non-Enhancing Tumor Tissue

Tumor tissue collected during Phase 0 surgery

Time frame
Intraoperatively
4

Phase 0: Median Unbound Concentration of BGB-58067 in Gadolinium Enhancing and Non-Enhancing Tumor Tissue

Tumor tissue collected during Phase 0 surgery

Time frame
Intraoperatively

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Nader Sanai

Lead sponsor

St. Joseph's Hospital and Medical Center, Phoenix

Sponsor institution

BeOne Medicines

Collaborator

Source ClinicalTrials.gov
Apply now